Coded mass spectroscopy methods, devices, systems and computer program products

ABSTRACT

A coded mass spectrometer incorporates a spatial or temporal code to reduce the resolution/sensitivity dichotomy inherent in mass spectrometry. The code is used to code one or more portions of a mass spectrometer. Coding patterns, such as Hadamard codes, Walsh codes, and perfect code sequences can be used. The coding can be spatial, for example, by using an aperture mask and/or temporal, for example, by coded injection of ions for analysis.

This application claims the benefit of U.S. Provisional Appln. No.60/644,356, filed Jan. 14, 2005, which is hereby incorporated byreference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Embodiments of the present invention relate to mass spectrometry. Moreparticularly embodiments of the present invention relate to using codedmass spectrometers to reduce the inherent trade off of resolution andsensitivity.

2. Background Information

Mass spectrometers generally operate by ionizing a sample, such as a gasanalyte. The ionized sample is generally filtered and the ions aretransported by electromotive forces toward a mass detector. The detectordetects the ions according to their mass-to-charge ratio through avariety of methods. Thus, the functional elements of a mass spectrometergenerally include ionization, mass separation, and ion detection.

FIG. 1 is a schematic diagram of an exemplary conventional massspectrometer 100. A gas analyte sample 102 is introduced to anionization chamber 104 between an emitter 106 and an extraction grid108. Ions are created through an ionization process in ionizationchamber 104. During the ionization process an electron may be removedfrom or added to gas analyte molecules. A portion of the moleculesintroduced into the ionization chamber are ionized. These ions have adistribution of velocities and directions, and are electromagneticallypulled through extraction grid 108 by operation of negatively biasedemitter 106 and a positively charge focus grid 110. A portion of theseions then pass through negatively biased acceleration grids 112. Enoughenergy is added by acceleration grids 112 that the ions that exit thegrid are collimated, as well as relatively homogeneous in momentum anddirection. These ions are then filtered through a slit to ensure thatthe remaining ions have originated from a single line in space. Thewidth of the slit, among other parameters, determines the resolution andsensitivity of the spectrometer. The thinner the slit, the better theresolution but the poorer the sensitivity.

As the ions move through the magnetic field, they are deflected basedupon their mass/charge ratio. Higher masses yield a lower deflection fora given charge. the ions strike a position sensitive detector 114.Detector 114 accumalates ion strike positions. This is read out as afunction of position, resulting in a mass spectrum. An exemplary massspectrum 200 is illustrated graphically in FIG. 2.

SUMMARY OF THE INVENTION

According to embodiments of the invention, devices, methods and computerprogram products are provided that incorporate coded spectroscopy in amass spectrometer. In some embodiments, an encoded pattern, such as aWalsh or Hadamard coding pattern or perfect coding sequence, is used tospatially encode portions of a mass spectrometer, e.g., by using a Walshor Hadamard encoded mask. In some embodiments, an encoded pattern isused to temporally encode a portion of a mass spectrometer, for example,by pulsing various elements of the mass spectrometer according to thecode. For example, electromagnetic fields used as part of thespectrometer may be pulsed on and off according to the encoded pattern.Detectors in the mass spectrometer may be encoded based on a spatialpattern (such as a mask) or based on a temporal pattern (such as bydetecting particles during intervals based on the coding pattern).

Embodiments of the present invention include computer program productsand/or hardware configured to implement a coded pattern in aconventional mass spectrometer, e.g., by controlling a temporal pattern,such as a pulsed electromagnetic field. Further embodiments of thepresent invention include mass spectrometers and other devices forintroducing coding patterns, such as with a masking pattern, a codedaperture array, a coded detector array, a coded focusing grid, and thelike. Coded electromagnetic fields and coded detectors may also be used.

Coded apertures may be used for the separation, analysis, sensing and/oridentification of charged particles and particles with mass. Thisincludes the coded apertures themselves, the algorithms required todesign the coding and to extract the desired information from the datagenerated using the coding, and the apparatus to take advantage of thecoded apertures. The embedded code and corresponding physicalinstruments may be used in systems that analyze particles that arecharged or have mass, in contrast to systems where coded apertures havebeen used to analyze particles without charge or mass, typically highenergy photons. Many kinds of atomic, molecular and ionic spectrometrycan utilize embedded codes to improve signal to noise ratio, enhanceresolution, and be physically simplified. Although embodiments of thepresent invention are described with respect to mass spectrometry, itshould be understood that any type of spectrometry using particles withmass and/or charge, such as electrons, atoms, molecules, etc. isconsidered within the scope of the invention. Examples of applicationfor encoded spectroscopy include the focusing of neutral oxygenmolecules for particle beam profiling and as a spatial and/or velocityfilter of neutral polar molecules for focusing and “cooling” of amolecular beam, or as a novel deposition method of molecules inMolecular Beam Epitaxy (MBE). In addition, embodiments of the inventioninclude both coded aperture imaging of these particles as well as codedaperture spectroscopy of such particles.

A mass spectrometer according to an embodiment of the present inventioncan provide:

-   -   1. application of aperture coding to charged particles or        particles with mass;    -   2. application of a temporal code rather than a spatial code;    -   3. application of aperture coding to mass spectrometry,        including magnetic sector mass spectrometry and time-of-flight        (TOF) mass spectrometry;    -   4. A larger sampling volume for the source particles to be used,        and as a result, the coded aperture can enable an array of        slits, rather than the single slit used currently, without        degrading resolution;    -   5. coded grids may be modified dynamically between spectra or        during collection, so that a particular component of the        spectrum may be emphasized or deemphasized by passing or        blocking particular particles (i.e., ions with a particular        mass/charge ratio in the case of classical mass spectrometry).    -   6. Combinations and subcombinations of 1-5 above.

Using embodiments of the invention, it may be possible to dramaticallyincrease output by reducing the number of particles lost in transit tothe detector. As a result, a coded mass spectrometer according to anembodiment of the present invention is likely to: (a) decrease the timeto acquire a spectrum, thereby reducing the power consumption, (b)increase the signal to noise ratio thereby enablg detection of peakspreviously too diffuse to detect, and/or (3) enable other features notpossible currently, such as isotope detection. The signal to noise ratiomay also be increased because of the increased number of particles. Theresolution of particles (mass/charge ratios in the case of massspectrometry) may also be increased because of an increase in signal tonoise. The coded apertures can allow the physical simplification of themeasurement apparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of an exemplary conventional massspectrometer.

FIG. 2 is a graphical illustration of an exemplary mass spectrumgenerated by the conventional mass spectrometer of FIG. 1.

FIG. 3 is a schematic diagram of a coded mass spectrometer according toan embodiment of the present invention.

FIG. 4 is a graphical illustration of the analysis region of an aperturecoded magnetic sector mass spectrometer according to an embodiment ofthe present invention.

FIG. 5 illustrates an exemplary implementation of a multiplexed massfilter according to an embodiment of the present invention.

FIG. 6 is a schematic diagram of an analysis region of a time-or-flightmass spectrometer according to an embodiment of the present invention.

FIG. 7 illustrates several ion pulses traveling toward a detector in amass spectrometer.

FIG. 8 is a schematic diagram of an analysis region of a coded massspectrometer combining aperture coding and injection time codingaccording to an embodiment of the present invention.

FIG. 9 is a schematic diagram of an analysis region of a coded magneticsector mass spectrometer according to an embodiment of the presentinvention.

FIG. 10 is a schematic diagram of a coded mass spectrometer using codingin the emitter and extraction grids according to an embodiment of thepresent invention.

FIGS. 11 a and 11 b are schematic diagrams of effusion time coded massspectrometers according to embodiments of the present invention.

FIG. 12 is a graph of an exemplary input mass spectrum for uric acid.

FIG. 13 is a schematic diagram of an exemplary input aperture mask usedfor position coding according to an embodiment of the present invention.

FIG. 14 is a graph comparing the reconstructed spectra for a massspectrometer using a slit aperture and a mass spectrometer using a codedaperture.

Before one or more embodiments of the invention are described in detail,one skilled in the art will appreciate that the invention is not limitedin its application to the details of construction, the arrangements ofcomponents, and the arrangement of steps set forth in the followingdetailed description or illustrated in the drawings. The invention iscapable of other embodiments and of being practiced or being carried outin various ways. Also, it is to be understood that the phraseology andterminology used herein is for the purpose of description and should notbe regarded as limiting.

DETAILED DESCRIPTION OF THE INVENTION

The present invention now will be described hereinafter with referenceto the accompanying drawings and examples, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein. Rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art.

A sensor can be understood fundamentally as an apparatus for convertinga physical input state into a sensor state, coupled with a technique forconverting that measurement into an estimate of the original inputstate. A sensor's measurement can be represented mathematically as{right arrow over (g)}=

{right arrow over (s)}+{right arrow over (n)}, where {right arrow over(s)} is the input state,

is the transformation matrix for the sensor, {right arrow over (n)}represents additive noise, and {right arrow over (g)} is the resultingsensor state. Estimation of the input state based on the sensor's outputis then {right arrow over (s)}_(est)=

{right arrow over (m)}, where

is the transformation matrix that represents the estimation process and{right arrow over (s)}_(est) is the resulting estimate of the inputstate. The simplest estimation uses

=

⁻.

In conventional mass-spectroscopy, the sensor state {right arrow over(g)} corresponds to a detector output. For example, the sensor state{right arrow over (g)} may correspond to either a charge density inspecific spatial locations (i.e., ions detected in the positionsensitive detector) for magnetic sector mass-spectroscopy, or chargearrival in a specific time period for time-of-flight mass-spectroscopy.Further, the transformation matrix

can be diagonal or nearly diagonal. This results in the well-knowntradeoff between resolution and sensitivity described above.

By contrast, according to embodiments of the invention, if theinstrument can be engineered such that the transformation matrix

has significant off-diagonal elements, then the resolution/sensitivitydichotomy can be reduced. A sensor with an off-diagonal transformationmatrix is referred to as a multiplex sensor.

A multiplex mass-spectrometer according to embodiments of the inventionmay reduce the resolution/sensitivity dichotomy. That is, as describedabove, a multiplex sensor may reduce or avoid the trade-off betweenresolution and sensitivity that is characteristic of conventional massspectrometers. Further, in a multiplex mass-spectrometer according toembodiments of the invention, the state estimate can be less sensitiveto additive noise processes because a multiplex approach can distributethe error more evenly across the system. The result may be reduced noisecontribution to the final state estimate. A multiplex mass-spectrometeraccording to embodiments of the invention may also result in fastermeasurements. Because the resolution/sensitivity tradeoff no longerholds, the device can be engineered to collect a greater sample. Ittherefore may achieve a given signal-to-noise ratio in a shorter timethan a conventional mass spectrometer. A multiplex transformation matrixaccording to embodiments of the invention may also allow for thepossibility of a compressive device where the number of elements in thestate reconstruction is greater than the number of elements in thesensor state. This can result in instruments that are smaller andcheaper than traditional instruments.

Any component of a mass spectrometer that contributes to the form of thetransformation matrix

can be incorporated into a coding scheme according to embodiments of thepresent invention. FIG. 3 is a schematic diagram of a coded massspectrometer 300 according to an embodiment of the present invention.Examples of the components of mass spectrometer 300 where coding may beuseful are illustrated in FIG. 3 and are listed below. For the purposeof brevity, these various coding elements are shown in the exemplarymass spectrometer of FIG. 3; however, it should be understood that oneor more of the coding elements may be used in various combinations. Insome embodiments, a single coding scheme is selected based on the needsof a particular application.

Coding may be introduced upon introduction of an analyte 302. The sampleto be analyzed may be introduced in a spatial and/or temporal codedpattern that interacts with another coded component or it may itself actas a dispersive element, e.g., through the relative effusion rates ofthe ions.

Coding may be introduced by an emitter 306. The emitters serve to ionizethe analyte, in this case a gas, in an ionization chamber 304 so thatthe ionized molecules can be influenced by the electromagnetic fields,which act to separate the ions according to mass. The emitter is thecathode of the emitter/extraction pair. The emitter may be coded toyield a smaller variation in ion momentum and direction, especially whenused in conjunction with another coded grid, such as the extractiongrid. Alternatively, it may simply be much larger than is possible in anuncoded system.

Coding may be introduced by an extraction grid 308. Extraction grid 308forms another part of the ionization chamber and acts as the anode. Itprovides a uniform field for the creation and extraction of the ions.This grid may be patterned spatially and/or pulsed temporally in a codedmanner and interact with any of the other grids.

Coding may be introduced by a focusing grid 310. As the ions exitextraction grid 308, they have a wide variation of momentum anddirection. Focusing grid 310 acts as an aperture, selecting a subset ofthe extracted ions based on direction. A coded focusing grid would allowa larger fraction of the extracted ions to be passed to the accelerationgrids.

Coding may be introduced by a longitudinal acceleration grid 312. Asions exit the focusing grid, they have a small distribution ofdirections, but still a large distribution of energy. The accelerationgrids add energy to the ions and homogenize their energy. The coding maybe embedded in this acceleration grid, or if the coding is accomplishedin other parts of the system, the grid may be designed to allow manymore ions to pass to the slit/coded aperture than is possible in anuncoded system.

Coding may be introduced by a transverse acceleration grid 311. Atransverse acceleration grid adds transverse kinetic energy to the ionsjust prior to their entrance into the analysis region. At its simplest,this grid focuses the ion trajectories, improving the performance ofother coding elements. Alternatively, the grid could code theorientation of the input velocity vectors.

Coding may be introduced by an aperture 313. In a typical system, thereis a slit that allows the starting position of the ions, in the magneticsector to be known precisely. This may be replaced with a coded aperturethat allows ions to pass in a way that can be decoded later, and whichmay be at an electric potential other than ground.

Coding may be introduced by a detector 314. The detection of the ionscan also be encoded. A position sensitive detector enables x and yposition to be determined and thus allows information on the particleposition that can be computationally decoded. Similarly, a physical codecan be embedded in this detector if desired and can be based on encodingelsewhere in the system.

Exemplary Applications of Coding to Mass-spectrometer Design

Embodiments of coded mass spectrometers according to the presentinvention are described below with respect to the following non-limitingexamples.

Aperture-coded Magnetic Sector Mass Spectrometer

In magnetic-sector mass-spectroscopy the ions are introduced into ananalysis region containing a transverse magnetic field. FIG. 4 is agraphical illustration of the analysis region of an aperture codedmagnetic sector mass spectrometer according to an embodiment of thepresent invention. Ions 402 entering analysis region 400 experience aLorentz force from a magnetic field 404 and travel along a circulartrajectory 406. Eventually, the ions impact a detector 408, and theircharge contributes to the signal.

Ions enter the analysis region a height z above the plane containing thedetector and has been accelerated by a potential in the x-direction ofV_(x). The detector starts at longitudinal position Ax and has positionsensitive resolution of width w at location i. The magnetic field istransverse to the ion motion and has magnitude B. For this arrangement,the signal contribution of an ion entering at height z to the i^(th)detector location is:

${g_{i}(z)} = {\int_{{\Delta\; x} + {{({i - 1})}w}}^{{\Delta\; x} + {iw}}{{\mathbb{d}x}{\int{{\mathbb{d}{{mS}(m)}}{\delta\left( {m - {\left( \frac{{qB}^{2}}{8V_{x}} \right)\left( \frac{\left( {x^{2} + z^{2}} \right)^{2}}{z^{2}} \right)}} \right)}}}}}$

The overall signal of the i^(th) detector location is then the integralof this term taken over all possible starting heights for the ion

${g_{i} \propto} = {\int{{\mathbb{d}{{zT}(z)}}{\int_{{\Delta\; x} + {{({i - 1})}w}}^{{\Delta\; x} + {iw}}{{\mathbb{d}x}{\int{{\mathbb{d}{{mS}(m)}}{\delta\left( {m - {\left( \frac{{qB}^{2}}{8V_{x}} \right)\left( \frac{\left( {x^{2} + z^{2}} \right)^{2}}{z^{2}} \right)}} \right)}}}}}}}$

Here T describes the transmission function on the input aperture. Atraditional instrument uses a slit aperture, so T(z)=δ(z−z_(s)), whichcollapses the first integral and makes the system description verysimple, although at the potential expense of throughput.

An alternative embodiment of the invention is to code the aperture withsome more complicated T. Exemplary codes include a code based on perfectsequences or a code based on a Hadamard code. An exemplary simulation ofa Hadamard coded system is presented herein. A Hadamard matrix is anyn×n matrix with elements in {−1,1 } with a maximal determinant. Noconstructive procedure for all Hadamard matrices is known, although itis conjectured that they exist for all n that are multiples of 4. Thereare constructive methods for subsets of the Hadamard matrices, the mostcommon being the Sylvester and Paley constructions. Numerous Hadamardmatrices of the sizes of interest for this application are known andhave been tabulated in the literature. Walsh functions are related tothe Hadamard matrices of order n=2^(m). When the rows and columns of theHadamard matrix are placed in sequency order (in sequential order basedon number of transitions), the rows of the Hadamard matrix are the Walshcodes of size n. A perfect sequence of length n is a sequence of numbersfor which the autocorrelation is zero except at values wheremod_(n)(x)=0.

FIG. 5 illustrates an exemplary implementation of a multiplexed massfilter. A one-dimensional position sensitive detector 502 captures ionsfrom the coded detector, effectively sampling a series of spectra 504that are displaced according to the ion position on the aperture. Thesignal is then deconvolved into a single spectrum 506.

Injection-time-coded Time-of-flight Mass Spectrometer

FIG. 6 is a schematic diagram of an analysis region 600 of atime-of-flight mass spectrometer according to an embodiment of thepresent invention. In time-of-flight mass-spectroscopy, ions 602 areintroduced into an analysis region after being accelerated by alongitudinal acceleration potential V_(x). The ion velocity after thisacceleration depends on the analyte mass. This variation in velocity dueto mass diffential leads to a longitudinal sorting of the masses as theypropagate through free space. After traveling a distance D, the ionsstrike a detector 604 on the far side of the analysis region.

The ions produce a time-varying current at the detector that depends onthe details of the mass-spectrum. The current can be written as:

${{g(t)} \propto {\int{{\mathbb{d}{{mS}(m)}}{\delta\left( {m - \left( \frac{2{{qV}_{x}\left( {t - t_{0}} \right)}^{2}}{D^{2}} \right)} \right)}}}},$where t₀ is the time at which the acceleration potential is turned on.

According to embodiments of the invention, this system may be coded intime by applying a series of acceleration pulses. The current at time tresulting from the i^(th) acceleration pulse is then

${g_{i}(t)} \propto {\int{{\mathbb{d}{{mS}(m)}}{{\delta\left( {m - \left( \frac{2{{qV}_{x,i}\left( {t - t_{\; 0}} \right)}^{2}}{D^{2}} \right)} \right)}.}}}$The total current at time t is then the sum of the contributions fromall of the pulses, and can be written as

${g(t)} \propto {\sum\limits_{i}{{{dmS}(m)}{{\delta\left( {m - \left( \frac{2{{qV}_{x,i}\left( {t - t_{\; 0}} \right)}^{2}}{D^{2}} \right)} \right)}.}}}$

Nominally g(t) consists of a sum of scaled and delayed mass spectra. Thechallenge of the sensor system is to decode these sums to produce theoriginal spectrum. FIG. 7 illustrates several ion pulses (Pulse 1, Pulse2, Pulse 3, Pulse 4, and Pulse 5) traveling to the detector. Thevertical displacement of the pulses is not physical and is included forclarity only. The detector signal at a time t is given by summing thevalues of all the pulses in the shaded band. If the presence/absence ofa pulse in the i^(th) pulse-slot is coded by the elements of a perfectsequence, the spectrum can be reconstructed from the temporal signalrecorded by the detector. In a discrete representation, if {right arrowover (g)} is a vector that contains the detected time-series, then:{right arrow over (g)}=

{right arrow over (g)} _(i).

For the case where

is a matrix whose rows are circularly-shifted versions of a perfectsequence, the inverse

=

⁻¹ exists and is well-conditioned. In that case the measurement thatwould have been obtained from a single ion pulse can be extracted by:{right arrow over (g)}=

⁻¹ {right arrow over (g)} _(i)=

⁻¹

{right arrow over (g)} _(i).This vector can then be converted into a mass spectrum using standardanalysis techniques of time-of-flight mass-spectroscopy.Hyperspectral Mass Spectrometer

The following embodiments of the present invention combine the elementsof the aperture-coded magnetic-sector and the injection-time-codedtime-of-flight mass-spectrometers described above. The result is ahigher-dimensional “data-volume” of spectral data. The data-volumecontains information on the analyte mass-spectrum as a function of bothspatial location and time. A device of this type is useful for analyzingspatio-temporal concentration dynamics of chemical processes. Further,the ability to track the time-rate-of-change of certain analytes (e.g.,common explosives) could be very important in security applications.

FIG. 8 is a schematic diagram of an analysis region 800 for aninstrument combining the elements of an aperture coded magnetic sectorinstrument and an injection-time-coded time-of-flight mass spectrometer.In this design, ions 802 enter analysis region 800. Analysis region 800contains a transverse magnetic field 804 of magnitude B. Aftertraversing this region, they strike a position sensitive detector 806 onthe far wall a distance D away.

For ions entering at a height z above a reference elevation, and for asingle pulse of acceleration potential, the contribution to the i^(th)detector location at time t is

${g_{i}\left( {z,t} \right)} \propto {\int_{{\Delta\; z} - {{({i + 1})}w}}^{{\Delta\; z} - {iw}}{{\mathbb{d}z^{\prime}}{\int{{\mathbb{d}{{mS}(m)}}{\delta\left( {m - {\left( \frac{{qB}^{2}}{8V_{x,i}} \right)\left( \frac{D^{2}}{\left( {z^{\prime} - z} \right)^{2}} \right)}} \right)}{{\delta\left( {m - \sqrt[3]{\frac{q^{3}B^{2}V_{x,i}t^{4}}{2\left( {z^{\prime} - z} \right)^{2}}}} \right)}.}}}}}$Considering all possible starting elevations, all acceleration pulses,and adding a transmission function T, we can write the totalcontribution to the i^(th) detector location as:

${g_{i}(t)} \propto {\sum\limits_{j}{\int{{\mathbb{d}{{zT}(z)}}{\int_{{\Delta\; z} - {{({i + 1})}w}}^{{\Delta\; z} - {iw}}{{\mathbb{d}z^{\prime}}{\int{{\mathbb{d}{{mS}(m)}}{\delta\left( {m - {\left( \frac{{qB}^{2}}{8V_{x,i}} \right)\left( \frac{D^{2}}{\left( {z^{\prime} - z} \right)^{2}} \right)}} \right)}{{\delta\left( {m - \sqrt[3]{\frac{q^{3}B^{2}{V_{x,j}\left( {t - t_{j}} \right)}^{4}}{2\left( {z^{\prime} - z} \right)^{2}}}} \right)}.}}}}}}}}$

In this scheme the detected signal is a sum of spectra that arestretched both spatially and temporally. For that reason, coding may beprovided in both the spatial and temporal domains in these embodiments.The presence/absence of an ion pulse is determined by the elements of aperfect sequence as described above for coded time-of-flightmass-spectroscopy, and the openings in the input aperture are determinedby either a perfect sequence or a Hadamard matrix as described above forcoded magnetic-sector mass-spectroscopy.

Mass Focused Magnetic-sector Mass-spectrometer

FIG. 9 is a schematic diagram of an analysis region 900 for a magneticsector mass spectrometer configured to minimize an ambiguity in theimpact location of an ion on the detector. In traditionalmagnetic-sector mass-spectroscopy, the impact location of the ion ontothe detector depends on both the charge-to-mass ratio of the ion and thevertical position of its entrance point into the analysis region. Thismultivariate dependence is the cause of the resolution/sensitivitydichotomy in a magnetic sector mass spectrometer. It is possible tominimize the ambiguity between the two variables by introducing atransverse acceleration grid that provides transverse kinetic energy tothe ion just prior to its entry into the analysis region.

The overall signal at location i in the detector is:

$g_{i} = {\int{{\mathbb{d}{{zT}(z)}}{\int_{{\Delta\; x} + {{({i - 1})}w}}^{{\Delta\; x} + {iw}}{{\mathbb{d}x}{\int{{\mathbb{d}{{mS}(m)}}{{\delta\left( {m - {\left( \frac{{qB}^{2}}{8} \right)\left( {\frac{\left( {x^{2} + z^{2}} \right)^{2}}{\left( {{V_{z}x^{2}} + {V_{x}z^{2}}} \right)} + \frac{2\sqrt{V_{x}V_{z}x^{2}{z^{2}\left( \left( {x^{2} + z^{2}} \right)^{4} \right)}}}{\left( {{V_{z}x^{2}} + {V_{x}z^{2}}} \right)^{2}}} \right)}} \right)}.}}}}}}}$This can be seen to reduce to the simpler magnetic-sector result abovefor the case where V_(x)=0.

With a proper transverse velocity, the impact location of the ionsdepends primarily on their charge-to-mass ratio and large inputapertures are possible without dramatically reducing the resolution ofthe instrument. Although such an arrangement could produce mass-spectraof reasonable resolution by itself, application of additional coding inthe system according to embodiments of the invention would furtherincrease the resolution of the instrument. The coding may take the formof a coded input aperture as in the coded magnetic-sectormass-spectroscopy.

Another combination according to embodiments of the invention is onethat combines the focusing effect with an aperture coding that could beturned on or off.

The system could produce a coarse mass-spectrum with the additionalcoding turned off. Then, if and when higher resolution was needed, thecoding could be activated, increasing the resolution of the device. Sucha setup would naturally provide a multi-scale view of the input state-alikely prerequisite for compressive sensing. Further, the ability forthe sensor to operate with limited capabilities with the coding turnedoff could have important applications for low-power applicationsdescribed below.

Ultra-low Power Mass Spectormeter

Coding in the emitter and extraction grids according to embodiments ofthe invention can yield a lower variation in the momentum and directionof the generated ions, allowing the focusing and acceleration grids tobe operated at much lower power or omitted altogether. FIG. 10 is aschematic diagram of a mass spectrometer according to an embodiment ofthe present invention using coding in the emitter and extraction grids.As shown ions in the emitter array plasma formed by ionization of thesample analyte are extracted through the extraction grid aperture array.As describe above, the ions pass through a magnetic field that deflectsthe ions onto a 2-dimensional detector array according to their masses.

As shown by graph 1002, the embodiment without acceleration grids canresult in a compressed spectrum as compared with the embodimentillustrated in FIG. 3. The compressed spectrum is due to the lowerenergies imparted to the ions due to the absence of the accelerationgrids. In addition, resolution may be limited as compared with theembodiment of the present invention illustrated in FIG. 3. However, theembodiment of FIG. 10 can result in detection of larger amu's, and/orlower power consumption.

Alternatively, some designs may allow the coding to be turned off untilthe system determines that higher resolution is necessary. Such anon-demand system according to embodiments of the invention could have adramatic impact on the power-requirements of the instrument. This lowerpower consumption may be highly desirable in many dispersed or portableapplications.

Effusion-time-coded Mass Spectrometer

FIG. 11 a is a schematic diagram of an effusion-time-coded massspectrometer 1100 according to an embodiment of the present invention.Ions 1102 from a plasma 1104 created during ionization effuse throughgas inlets 1106 a-e. Gas inlets 1106 a-e are an array of tiny pinholesbetween high density plasma 1102 and a time of flight detector 1108. Acoded aperture 1110 between the effusion of ions 1102 and detector array1108 provides mass spectrometer coding according to position. Theeffusion rate is a function of the mass of the ion. Lighter ions effusemore quickly, according to Graham's law:(effusion rate)_(A)×(molecular mass)_(A) ^(1/2)=(effusionrate)_(B)×(molecular mass)_(B) ^(1/2)Time-domain coding could be added to the arrangement illustrated in FIG.11 by opening and closing gas inlets 1106 a-e in a coded manner at acertain frequency, to correct for the quantum efficiency of thedetector.

FIG. 11 b is a schematic diagram of an effusion-time-codedtime-of-flight mass spectrometer 1150 according to an embodiment of thepresent invention. A plasma 1104 containing ions 1102 is created duringionization of a sample, such as a gas analyte. Ions 1102 are effused togas inlets 1106 a-e. Gas inlets 1106 a-e are opened and closed accordingto a temporal coding sequence, such as shown by creation/collectionpulse train 1154. As is typical in time-of-flight mass spectrometers,ions 1102 are accelerated toward a position coded aperture 1110 and adetector 1108 by acceleration grids 1152 a and 1152 b. The ions drifttoward position coded aperture 1110 through a free drift region 1156.Ions with higher mass-to-charge ratios, such as ion 1158, take longer toreach coded aperture 1110 than ions with lower mass-to-charge ratios,such as ion 1160.

Accelerator grids 1152 a and 1152 b may not be necessary in thetime-of-flight mass spectrometer illustrated in FIG. 11 b. This isbecause a dispersive element separates the ions according to mass/chargeratio and the time-domain coding will separate the ions according toinlet of origin. Consequently, the embodiment of the present inventionillustrated in 11 a may be sufficient for a time-of-flight massspectrometer according to an embodiment of the present invention aswell.

Sample Design for an Aperture-coded Magnetic Sector Mass Spectrometer

Following is an examination of one of the designs described above.Specifically, an exemplary implementation of an aperture-codedmagnetic-sector mass spectrometer according to an embodiment of thepresent invention as well as how it achieves both high-resolution andhigh sensitivity is discussed below.

A general schematic for the analysis region of a magnetic sector massspectrometer is provided in FIG. 4. An exemplary magnetic sector massspectrometer has an ionization region of transverse dimensions 10 mm (y)and 1 mm(z). The longitudinal acceleration grid has a potentialdifference of 100V, and the magnetic field strength is 0.5 T, and isoriented in the -y direction. The detector is located 1 mm below theionization region and has a transverse extent that matches theionization region. Longitudinally, the detector extends from 4-13 mmfrom the input aperture. The position sensitive detector can distinguish192 locations in the transverse direction and 500 locations in thelongitudinal direction.

For comparison purposes, the performance of two different inputapertures is simulated as follows: 1) a horizontal slit of height 10.4microns located at the bottom of the input aperture, and 2) a codedaperture based on the order-96 Hadamard matrix. The slit represents theapproach used in conventional instruments, while the coded aperture isan embodiment of the present invention. In each case, the trajectory of10⁶ ions are simulated and traced through the apparatus to determinetheir contribution to the signal from the position sensitive detector.The ions are drawn from a probability distribution that accuratelyreflects the mass-spectrum of uric acid, and therefore represents anaccurate simulation on how the various designs would fare in detectingthis particular compound. FIG. 12 is a graph 1200 of an exemplary inputmass spectrum for uric acid.

FIG. 13 is a schematic of the exemplary input aperture mask used forposition coding in the present example. The white regions of aperturemask 1300 indicate areas that are transmissive to ions. The blackregions of aperture mask 1300 indicate areas that block the ions.

FIG. 14 is a graph 1400 comparing the reconstructed spectrum for theslit aperture 1402 and the spectrum for the coded aperture 1404 with theinput spectrum 1406. The signal from the slit has been numericallymultiplied by a factor of 50 to make it comparable to the signal fromthe coded mask-indicating that the coded aperture achieves a throughputadvantage of 50 as expected. The correspondence between the tworeconstructions and the input spectrum is quite good. Bothreconstructions show some deviation from the input spectrum, mostnotably at high-amus. These deviations arise from the discrete nature ofthe position sensitive detector and can be corrected by software.

Embodiments according to the invention include the application of codingto any sensor that is based on particle separation, where the particlehas a finite mass and the separation is accomplished in the spatialdomain and/or in the time domain.

Embodiments of the present invention have been described with referenceto block diagrams and/or flowchart illustrations of methods, apparatus(systems) and/or computer program products according to embodiments ofthe invention. It is understood that each block of the block diagramsand/or flowchart illustrations, and combinations of blocks in the blockdiagrams and/or flowchart illustrations, can be implemented by computerprogram instructions. These computer program instructions may beprovided to a processor of a general purpose computer, special purposecomputer, and/or other programmable data processing apparatus to producea machine, such that the instructions, which execute via the processorof the computer and/or other programmable data processing apparatus,create means for implementing the functions/acts specified in the blockdiagrams and/or flowchart block or blocks.

These computer program instructions may also be stored in acomputer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory produce an article of manufacture including instructions whichimplement the function/act specified in the block diagrams and/orflowchart block or blocks.

The computer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer-implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions/acts specified inthe block diagrams and/or flowchart block or blocks.

Accordingly, the present invention may be embodied in hardware and/or insoftware (including firmware, resident software, micro-code, etc.).Furthermore, the present invention may take the fouls of a computerprogram product on a computer-usable or computer-readable storage mediumhaving computer-usable or computer-readable program code embodied in themedium for use by or in connection with an instruction execution system.

In the context of this document, a computer-usable or computer-readablemedium may be any medium that can contain, store, communicate,propagate, or transport the program for use by or in connection with theinstruction execution system, apparatus, or device.

The computer-usable or computer-readable medium may be, for example butnot limited to, an electronic, magnetic, optical, electromagnetic,infrared, or semiconductor system, apparatus, device, or propagationmedium. More specific examples (a non-exhaustive list) of thecomputer-readable medium would include the following: an electricalconnection having one or more wires, a portable computer diskette, arandom access memory (RAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), an optical fiber,and a portable compact disc read-only memory (CD-ROM). Note that thecomputer-usable or computer-readable medium could even be paper oranother suitable medium upon which the program is printed, as theprogram can be electronically captured, via, for instance, opticalscanning of the paper or other medium, then compiled, interpreted, orotherwise processed in a suitable manner, if necessary, and then storedin a computer memory.

As used to describe embodiments of the present invention, the term“coupled” encompasses a direct connection, an indirect connection, or acombination thereof. Two devices that are coupled can engage in directcommunications, in indirect communications, or a combination thereof.Moreover, two devices that are coupled need not be in continuouscommunication, but can be in communication typically, periodically,intermittently, sporadically, occasionally, and so on. Further, the term“communication” is not limited to direct communication, but alsoincludes indirect communication.

In the foregoing detailed description, systems and methods in accordancewith embodiments of the present invention have been described withreference to specific exemplary embodiments. Accordingly, the presentspecification and figures are to be regarded as illustrative rather thanrestrictive. The scope of the invention is to be further understood bythe numbered examples appended hereto, and by their equivalents.

1. A coded mass spectrometer, comprising: an ion source to generate ionsfrom a sample; a detector to detect a plurality of mass-to-charge ratiosassociated with the ions; one or more grids located between the ionsource and the detector, that cause the ions to travel toward thedetector, and that reduce a variation of momentum and directionattributable to the ions; and a code applied by one or more of the ionsource, the one or more grids, and the detector and representedmathematically by a transformation matrix comprising at least oneoff-diagonal element, wherein a mass spectrum of the ions is calculatedfrom the plurality of mass-to-charge ratios and the transformationmatrix.
 2. The coded mass spectrometer of claim 1, wherein the code is aspatial code.
 3. The coded mass spectrometer of claim 1, wherein thecode is a temporal code.
 4. The coded mass spectrometer of claim 1,wherein the coded mass spectrometer is a magnetic sector massspectrometer having a magnetic field that affects the travel of theions.
 5. The coded mass spectrometer of claim 1, wherein the coded massspectrometer is a time-of-flight mass spectrometer.
 6. The coded massspectrometer of claim 1, wherein the code is provided by injections ofions according to a time code.
 7. The coded mass spectrometer of claim1, wherein the ion source comprises an emitter, and the code is suppliedby the emitter to lower variation in a momentum and a direction of theions.
 8. The coded mass spectrometer of claim 1, wherein the codecomprises a Hadamard code.
 9. The coded mass spectrometer of claim 1,wherein the code comprises a Walsh code.
 10. The coded mass spectrometerof claim 1, wherein the code comprises a perfect coding sequence.
 11. Acoded mass spectrometer, comprising: an ion source to generate ions froma sample; a coded aperture; one or more grids located between the ionsource and the coded aperture, that cause the ions to travel toward thecoded aperture, and that reduce a variation of momentum and directionattributable to the ions; a detector that receives the ions from thecoded aperture and detects a plurality of mass-to-charge ratiosassociated with the ions; and a code applied by the coded aperture andrepresented mathematically by a transformation matrix comprising atleast one off-diagonal element, wherein a mass spectrum of the ions iscalculated from the plurality of mass-to-charge ratios and thetransformation matrix.
 12. A method of estimating a mass spectrum of asample using a coded mass spectrometer, comprising: generating ions fromthe sample using an ion source; causing the ions to travel toward adetector and reducing a variation of momentum and direction attributableto the ions using one or more grids; applying a code to the ions that isrepresented mathematically by a transformation matrix comprising atleast one off-diagonal element; detecting a plurality of mass-to-chargeratios associated with the ions using the detector; and calculating themass spectrum from the plurality of mass-to-charge ratios and thetransformation matrix.
 13. The method of claim 12, wherein the code is aspatial code.
 14. The method of claim 12, wherein the code is a temporalcode.
 15. The method of claim 12, wherein the coded mass spectrometer isa time-of-flight mass spectrometer.
 16. The method of claim 12, whereinthe code is applied to the ions using the ion source.
 17. The method ofclaim 12, wherein the code is applied to the ions using the one or moregrids.
 18. The method of claim 12, wherein the code is applied to theions using the detector.
 19. The method of claim 12, wherein the code isapplied to the ions using a coded aperture.
 20. The method of claim 12,wherein a number of elements in the mass spectrum is greater than theplurality of mass-to-charge ratios detected.